title: PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients: a systematic review.
abstract: BACKGROUND
  Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed.
  
  
  METHODS
  Using terms for PTGS2 and colorectal cancer, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled HRs [95% confidence intervals (CI)] for the association between PTGS2 expression and tumor recurrence, colorectal cancer-specific survival, and overall survival.
  
  
  RESULTS
  In total, 29 studies, which had prognostic data on 5,648 patients, met the inclusion criteria. PTGS2-positive patients were at an increased risk of tumor recurrence (n = 9 studies; HR, 2.79; 95% CI, 1.76-4.41; P < 0.001) and had poorer colorectal cancer-specific survival (n = 7; HR, 1.36; 95% CI, 1.02-1.82; P = 0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancer-specific survival but less so for recurrence. PTGS2 expression was not associated with overall survival [(n = 16; pooled unadjusted HR, 1.30; 95% CI, 0.94-1.79; P = 0.11) and (n = 9; pooled adjusted HR, 1.02; 95% CI, 0.72-1.45; P = 0.91)].
  
  
  CONCLUSIONS
  PTGS2 expression was associated with an increased risk of tumor recurrence and poorer colorectal cancer-specific survival but not overall survival among patients with colorectal cancer. However, confounding by tumor characteristics such as tumor stage seems likely.
  
  
  CONCLUSIONS
  There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in patients with colorectal cancer. Furthermore, studies providing adjusted results are required.
authors.affiliation: Centre of Excellence for Public Health North Ireland, Queen's University Belfast, Belfast, Northern Ireland. akunzmann01@qub.ac.uk
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Kunzmann
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murray
authors.forename: Chris R
authors.initials: CR
authors.lastname: Cardwell
authors.forename: Charlene M
authors.initials: CM
authors.lastname: McShane
authors.forename: Una C
authors.initials: UC
authors.lastname: McMenamin
authors.forename: Marie M
authors.initials: MM
authors.lastname: Cantwell
mesh_terms: D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D006801:Humans; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human